Gym-based aerobic exercise with bicycle ergometer contributes to the regression of human papilloma virus infection: a single-center, single-blind and randomized controlled trial

The regression of human papilloma virus is multifactorial and could be possibly targeted by using life-mode form of intervention. The purpose of this trial is to clarify the effect of aerobic exercise on the regression in outpatients firstly diagnosed with human papilloma virus(HPV) infection. Patients were randomly allocated into exercise group (Arm A) and control group (Arm B). Patients in Arm A received the 45-minute aerobic exercise thrice per week using the bicycle ergometer at gym. Patients in Arm B received their usual care at home. The physical exercise spanned a period of 6 weeks. The characteristics at baseline were documented and HPV specimens were tested at initiation, three months and six months after project launching. The primary endpoint was current HPV infection incidents as well as stratified by age at 3-months and 6-months. The secondary endpoint was newly diagnosed HPV incidents.In total, 125 patients in arm A and 136 patients in arm B were enrolled. The mean follow-up period was 7.5 ± 1.5 months (range 6.0–9.2). Post physical training, no significant difference of HPV 16/18 in groups was observed at 3-months or 6-months. As to current rate, physical exercise was superior to the patients with non-16/18 high-risk human papilloma virus(HR-HPV) infections at 6-months (p = 0.01). Stratified by age, the strength was still strong regarding age span of 18–25 years, 30–35 years, 35–45 years (p = 0.02, p = 0.04, p = 0.01, respectively). Additionally, the newly diagnosed HPV infection (HPV16/18 excluded) significantly decreased from 29 (21.3%) in Arm B to 14 (11.2%) in Arm A (p = 0.02). The current trail indicates that the 6-week aerobic exercise positively affects the regression of HPV infection, especially regarding the non-16/18 HPV infection.

Aerobic exercise; Human papilloma virus; Cervical cancer; Regression

[1] Hooi DJ, Lissenberg-Witte BI, Kenter G, de Koning MNC, Gomes Bravio I, Ardts K, et al. Human papillomavirus (HPV) prevalence and associated risk factors in women from Curaçao. PLoS One. 2018; 13: e199624.

[2] Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012; 30: F12–F23.

[3] Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta‐analysis of 1 million women with normal cytological findings. The Journal of Infectious Diseases. 2010; 202: 1789–1799.

[4] Byun JM, Jeong DH, Kim YN, Jung EJ, Lee KB, Sung MS, et al. Persistent HPV-16 infection leads to recurrence of high-grade cervical intraepithelial neoplasia. Medicine. 2018; 97: e13606.

[5] Cecchini S, Carozzi F, Confortini M, Zappa M, Ciatto S. Persistent human papilloma virus infection as an indicator of risk of recurrence of high-grade cervical intraepithelial neoplasia treated by the loop electrosurgical excision procedure. Tumori Journal. 2004; 90: 225–228.

[6] Zheng Z, Yang X, Yao X, Li L. Prognostic value of HPV 16/18 genotyping and geminin mRNA quantification in low-grade cervical squamous intraepithelial lesion. Bioengineered. 2021; 12: 11482–11489.

[7] Maldonado Alvarado E, Osorio Peralta MO, Moreno Vázquez A, Martínez Guzmán LA, Melo Petrone ME, Enriquez Mar ZI, et al. Effectiveness of photodynamic therapy in elimination of HPV-16 and HPV-18 Associated with CIN I in mexican women. Photochemistry and Photobiology. 2017; 93: 1269–1275.

[8] Hu Z, Liu L, Zhang W, Liu H, Li J, Jiang L, et al. Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts. Photodiagnosis and Photodynamic Therapy. 2018; 21: 86–90.

[9] Su Y, Zhang M, Zhang W, Shi H. Clinical efficacy of cryotherapy combined with interferon in the treatment of chronic cervicitis complicated with HPV infection. Pakistan Journal of Pharmaceutical Sciences. 2017; 30: 1505–1508.

[10] Penko A L, Zimmerman N M, Crawford M, Linder SM, Alberts JL. Effect of AE on cardiopulmonary responses and predictors of change in individuals with parkinson’s disease. Archives of Physical Medicine and Rehabilitation. 2021; 102: 925–931.

[11] Aburub A, Ledger SJ, Sim J, Hunter SM. Cardiopulmonary function and AE in parkinson’s: a systematic review of the literature. Movement Disorders Clinical Practice. 2020; 7: 599–606.

[12] Yaping X, Huifen Z, Meijing Z, Huibin H, Chunhong L, Fengfeng H, et al. Effects of moderate-intensity AE on blood glucose levels and pregnancy outcomes in patients with gestational diabetes mellitus: a randomized controlled trial. Diabetes Therapy. 2021; 12: 2585–2598.

[13] Baghaiee B, Karimi P, Ebrahimi K, Dabagh Nikoo Kheslat S, Sadeghi Zali MH, Daneshian Moghaddam AM, et al. Effects of a 12-week AE on markers of hypertension in men. Journal of Cardiovascular and Thoracic Research. 2018; 10: 162–168.

[14] Chiang S, Heitkemper MM, Hung Y, Tzeng W, Lee M, Lin C. Effects of a 12- week moderate-intensity exercise training on blood glucose response in patients with type 2 diabetes. Medicine. 2019; 98: e16860.

[15] Lee VY, Booy R, Skinner R, Edwards KM. The effect of exercise on vaccine-related pain, anxiety and fear during HPV vaccinations in adolescents. Vaccine. 2018; 36: 3254–3259.

[16] Shiri R, Coggon D, Falah-Hassani K. Exercise for the prevention of low back and pelvic girdle pain in pregnancy: a meta-analysis of randomized controlled trials. European Journal of Pain. 2018; 22: 19–27.

[17] Keller K, Ramos-Cartagena JM, Guiot HM, Muñoz C, Rodríguez Y, Colón-López V, et al. Association of smoking with anal high-risk HPV infection and histologically confirmed anal high-grade squamous intraepithelial lesions among a clinic-based population in Puerto Rico. Cancer Treatment and Research Communications. 2022; 30: 100503.

[18] Roset Bahmanyar E, Paavonen J, Naud P, Salmerón J, Chow S, Apter D, et al. Prevalence and risk factors for cervical HPV infection and abnormalities in young adult women at enrolment in the multinational PATRICIA trial. Gynecologic Oncology. 2012; 127: 440–450.

[19] Liang W. Condom use and the risk of HPV infection. New England Journal of Medicine. 2006; 355: 1388–1389.

[20] Giannella L, Giorgi Rossi P, Delli Carpini G, Di Giuseppe J, Bogani G, Gardella B, et al. Age-related distribution of uncommon HPV genotypes in cervical intraepithelial neoplasia grade 3. Gynecologic Oncology. 2021; 161: 741–747.

[21] Rebolj M, Mathews CS, Pesola F, Cuschieri K, Denton K, Kitchener H, et al. Age-specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot. British Journal of Obstetrics and Gynaecology. 2022; 129: 1278–1288.

[22] Giannella L, Fodero C, Boselli F, Rubino T, Mfuta K, Prandi S. Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia. Inter-national Journal of Gynecology & Obstetrics. 2017; 137: 72–77.

[23] Wedell-Neergaard A, Lang Lehrskov L, Christensen RH, Legaard GE, Dorph E, Larsen MK, et al. Exercise-induced changes in visceral adipose tissue mass are regulated by il-6 signaling: a randomized controlled trial. Cell Metabolism. 2019; 29: 844–855.e3.

[24] Chen X, Li H, Wang K, Liang X, Wang W, Hu X, et al. AE ameliorates myocardial inflammation, fibrosis and apoptosis in high-fat-diet rats by inhibiting P2X7 purinergic receptors. Frontiers in Physiology. 2019; 10: 1286.

[25] Li N, Yang C, Xie H, Liu Y, Liao Y. Effects of aerobic exercise on rats with hyperandrogenic polycystic ovarian syndrome. International Journal of Endocrinology. 2021; 2021: 1–12.

[26] Qiu F, Yuan C, Xu J, Zhang J, Chen F, Liu D, et al. Role of B7-H4 in the progression and prognosis of cervical inflammation to cancer after human papilloma virus infection. Journal of Biomedical Nanotechnology. 2019; 15: 1043–1051.